The objectives of this research are to produce biochemical models of mental retardation syndromes in laboratory animals by chemical means. By a study of the mechanisms by which specific chemical alterations produce changes in normal neural functioning, it is hoped that new methods for preventing such alterations may be found, thus pointing the way for new clinical approaches. Recently, it has been shown that treatment of newborn rats with p-chlorophenylalanine plus phenylalanine produces a biochemical picture similar to that seen in clinical phenylketonuria and that such treatment during the development of the rat produces, in the adult animal, behavioral and pathological changes similar to those seen in adult human beings suffering from phenylketonuria. Current studies are directed toward: (1) discovering a treatment which will prevent or reverse the behavioral changes seen in the model; (2) exploring the use of other, less toxic inhibitors; (3) pinpointing the exact developmental period of the insult.